Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy
Jose A Muñoz-Moreno, Sara Carrillo-Molina, Ignacio Martínez-Zalacaín, Cristina Miranda, Christian Manzardo, Pep Coll, Michael Meulbroek, Tomáš Hanke, Maite Garolera, Josep M Miró, Christian Brander, Bonaventura Clotet, Carles Soriano-Mas, José Moltó, Beatriz Mothe; BCN02-Neuro Substudy Group
ABSTRACT
Objective: To assess the central nervous system (CNS) impact of a kick&kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent.Design: Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks.Methods: Substudy participation was offered to all BCN02 participants (N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited (n = 10). Primary endpoint was change in a global cognitive score (NPZ-6).Results: Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks (n = 3) and those who resumed therapy for 24 weeks (n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints.Conclusion: No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP.AIDS. 2022 Mar 1;36(3):363-372. doi: 10.1097/QAD.0000000000003121. PMID: 34750296.
View: https://journals.lww.com/aidsonline/fulltext/2022/03010/preserved_central_nervous_system_functioning_after.5.aspx
Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy
Jose A Muñoz-Moreno, Sara Carrillo-Molina, Ignacio Martínez-Zalacaín, Cristina Miranda, Christian Manzardo, Pep Coll, Michael Meulbroek, Tomáš Hanke, Maite Garolera, Josep M Miró, Christian Brander, Bonaventura Clotet, Carles Soriano-Mas, José Moltó, Beatriz Mothe; BCN02-Neuro Substudy Group
ABSTRACT
Objective: To assess the central nervous system (CNS) impact of a kick&kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent.Design: Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks.Methods: Substudy participation was offered to all BCN02 participants (N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited (n = 10). Primary endpoint was change in a global cognitive score (NPZ-6).Results: Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks (n = 3) and those who resumed therapy for 24 weeks (n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints.Conclusion: No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP.AIDS. 2022 Mar 1;36(3):363-372. doi: 10.1097/QAD.0000000000003121. PMID: 34750296.
Curr Alzheimer Res. 2020;17(2):158-167. doi: 10.2174/1567205017666200317093341. PMID: 32183672.
